This study uses well characterized proteins for which the native sequence and structure is known for a number of species to address two important aspects of the recognition of protein antigens by immunoglobulin receptors. The first is concerned with the conformational features of the molecular surface that determines the recognition of protein determinants by B cells as well as the ability of determinants to interact with antibodies. The second is the mechanism by which protein determinants bind to the immunoglobulin receptor and the influence of such binding on determinant conformation. Initially, this study will concentrate on a careful delineation of the antigenic determinants of cytochrome c but in later stages we will test the generality of our findings with pancreatic polypeptide. Antigenic determinants will be determined for cytochrome c by applying theoretical and experimental techniques to locations in the molecule suggested by published structural and immunological data. We will visually appraise the surface structure of the protein using computer graphics to select possible antigenic peptide sequences. Conformational energy calculations on these peptides will determine the stability of their native conformation when absent from the native molecule. The peptides will be synthesized on a macroreticular resin so that their antigenicity can be checked at each amino acid coupling to determine the minimum sequence required for binding to antibody. The immunogenicity of the peptides will be established prior to a rigorous conformational analysis experimentally using physico-chemical techniques and theoretically with conformational energy calculations.